Topographic maps are the means by which all sensory systems process afferent information. Hence, understanding how topographic maps develop is a pressing issue in neurobiology. Classically, the projection of retinal axons to the brain has provided a model for the investigation of neural maps. However, in recent years the olfactory map has attracted increasing attention because of its distinct wiring pattern. Olfactory neurons responsive to different odors are interspersed in the receptor sheet. Yet they project their axons with great precision to specific targets (glomeruli) in the brain. Due to its distinct connectivity, studying the olfactory map promises to yield insights that contrast with those of the retinotopic map. Despite intense interests, the developmental origin of the olfactory map remains mysterious. The long-term goal of my laboratory is to elucidate the mechanisms of neurite guidance and olfactory map development, using the Drosophila antennal lobe as a model system. Our preliminary data indicated that the Wnt5 signaling protein and its receptor, Derailed, are required for the development of the glomerular pattern. In this proposal, we hypothesize that Wnt5 is an organizer of the early fly olfactory map and that special guidepost cells express the Wnt5 protein. Furthermore we postulate that Derailed acts as a novel extracellular regulator of Wnt5. Our specific Aims are to: (1) Characterize the function and source of Wnt5 in antennal lobe development. This will be carried out through constructions of special markers that label the guidepost cells and detailed phenotypic analyses of the cells using the markers. (2) Establish that Derailed is a novel extracellular regulator of Wnt5. This will be achieved through a structure-function study of the Derailed protein and epistatic analyses of the wnt5 and derailed genes during antennal lobe development. These experiments are expected to provide critical insights into the earliest stages of olfactory map development. PUBLIC HEALTH RELEVANCE: The olfactory map is essential for the processing of smell information. Thus, understanding the mechanisms that construct the map is a major goal in neuroscience. This AREA proposal will contribute to the unraveling of the long-standing enigma of the developmental origin of the olfactory map, and thus increases our understanding of how the brain processes smell.